# Single-cell inflammatory signaling defines a novel CEP135+ endothelial subtype associated with glioma progression

## TL;DR

A new type of inflammation-linked blood vessel cell in brain tumors is identified, marked by CEP135, and linked to worse patient outcomes.

## Contribution

Discovery of a novel CEP135+ endothelial cell subtype in gliomas and its association with inflammation and poor prognosis.

## Key findings

- A CEP135+ endothelial subtype with high inflammatory signaling is identified in gliomas.
- CEP135 expression correlates with advanced tumor grade and poor survival in glioma patients.
- Inflammatory endothelial reprogramming is dynamically induced during glioma progression.

## Abstract

•Single-cell multi-omics analysis reveals a previously unrecognized inflammation-high endothelial cell subtype in glioma.•This endothelial subtype is characterized by strong activation of interferon response, IL6/JAK/STAT3 signaling, and complement pathways.•Trajectory and cell–cell communication analyses indicate that inflammatory endothelial reprogramming is dynamically induced during glioma progression.•CEP135 is identified as a highly specific marker of inflammation-associated endothelial cells and is validated across transcriptomic, proteomic, and tissue levels.•High CEP135 expression correlates with advanced tumor grade, poor treatment response, and unfavorable survival outcomes in glioma patients.

Single-cell multi-omics analysis reveals a previously unrecognized inflammation-high endothelial cell subtype in glioma.

This endothelial subtype is characterized by strong activation of interferon response, IL6/JAK/STAT3 signaling, and complement pathways.

Trajectory and cell–cell communication analyses indicate that inflammatory endothelial reprogramming is dynamically induced during glioma progression.

CEP135 is identified as a highly specific marker of inflammation-associated endothelial cells and is validated across transcriptomic, proteomic, and tissue levels.

High CEP135 expression correlates with advanced tumor grade, poor treatment response, and unfavorable survival outcomes in glioma patients.

Chronic inflammation is a key driver of glioma progression, but its cellular organization within the tumor microenvironment remains poorly understood.

This study employed an integrated multi-omics analysis strategy, combining bulk transcriptomics, proteomics, and glioma cell line expression data with single-cell RNA sequencing data from paired gliomas and adjacent normal brain tissues. Inflammatory signaling activity was quantitatively assessed using pathway-level scoring methods, endothelial cell heterogeneity was analyzed at single-cell resolution, and pseudo-temporal trajectory analysis and cell-cell communication analysis were further conducted. Immunohistochemical analysis was performed using human glioma brain tissue samples from our center to independently validate key findings at the protein level.

Bulk transcriptomics analysis revealed significantly activated inflammatory signals in glioblastomas. Single-cell analysis identified a highly inflammatory endothelial cell subtype that was significantly enriched in tumor tissues. Cell communication analysis further revealed enhanced signal output capabilities and participation in neurally-related ligand-receptor interactions. CEP135 was specifically enriched in this endothelial cell subtype and showed consistent upregulation of both transcriptional and protein levels across multiple independent datasets. Immunohistochemical analysis of glioma brain tissue from our center confirmed that CEP135 is primarily localized in tumor-associated endothelial regions, and its expression level was significantly correlated with increasing tumor grade.High CEP135 expression was associated with poor treatment response, shorter survival outcomes.

This study identified a innovative CEP135+inflammation-associated endothelial cell subtype and established CEP135 as a key biomarker linking endothelial inflammation reprogramming, tumor progression, and adverse clinical outcomes.

Image, graphical abstract